Letter | Published:

Phagocytic activity of neuronal progenitors regulates adult neurogenesis

Nature Cell Biology volume 13, pages 10761083 (2011) | Download Citation

Abstract

Whereas thousands of new neurons are generated daily during adult life, only a fraction of them survive and become part of neural circuits; the rest die, and their corpses are presumably cleared by resident phagocytes. How the dying neurons are removed and how such clearance influences neurogenesis are not well understood. Here, we identify an unexpected phagocytic role for the doublecortin (DCX)-positive neuronal progenitor cells during adult neurogenesis. Our in vivo andex vivo studies demonstrate that DCX+ cells comprise a significant phagocytic population within the neurogenic zones. Intracellular engulfment protein ELMO1, which promotes Rac activation downstream of phagocytic receptors, was required for phagocytosis by DCX+ cells. Disruption of engulfment in vivo genetically (in Elmo1-null mice) or pharmacologically (in wild-type mice) led to reduced uptake by DCX+ cells, accumulation of apoptotic nuclei in the neurogenic niches and impaired neurogenesis. Collectively, these findings indicate a paradigm wherein DCX+ neuronal precursors also serve as phagocytes, and that their phagocytic activity critically contributes to neurogenesis in the adult brain.

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Acknowledgements

We thank S. Smith for editing the original version of the manuscript and S. Zeitlin for comments. We also thank the members of the Kipnis and Ravichandran laboratories for discussions at many stages of conducting the work and the preparation of the manuscript. This work was supported in part by an award from the National Institute of General Medical Sciences (GM55761) to K.S.R. and in part by an award from the National Institute on Aging (R01AG034113) to J.K. K.S.R. is a Bill Benter Senior Fellow of the American Asthma Foundation.

Author information

Author notes

    • Yubo Chen

    Present address: Key Laboratory for NeuroInformation of Ministry of Education, University of Electonic Science and Technology of China, ChengDu, 610054, China

Affiliations

  1. Department of Neuroscience, University of Virginia, Charlottesville, Virginia 22901, USA

    • Zhenjie Lu
    • , Yubo Chen
    • , James T. Walsh
    •  & Jonathan Kipnis
  2. Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22901, USA

    • Michael R. Elliott
    •  & Kodi S. Ravichandran
  3. Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia 22901, USA

    • Alexander L. Klibanov
  4. Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22901, USA

    • Kodi S. Ravichandran

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Contributions

Z.L. participated in the experimental design, carried out most of the experiments, analysed the data and participated in manuscript preparation; M.R.E. assisted with phagocytic assays and participated in experimental design; Y.C. assisted with immunofluorescent experiments; J.T.W. assisted with intracranial injections; A.L.K. supplied all the liposomes used in this study; K.S.R. helped with design of experiments and prepared the manuscript; J.K. designed the experiments, assisted with data analysis and prepared the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Yubo Chen or Kodi S. Ravichandran or Jonathan Kipnis.

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DOI

https://doi.org/10.1038/ncb2299

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